Psoriasis is a common chronic skin disease whose cause is unknown. It is characterized by persistent patches of redness covered with scales. The disease is in part determined by a genetically dominant trait. While it is absent at birth, it can begin at any age from childhood to extreme old age. Psoriasis does not, however, appear to be a communicable disease and there are no known causative factors for it in the environment.
In the involved patches, the cells of the epidermis grow and multiply up to seven times faster than normal. The agents currently used for treatment of psoriasis include ultraviolet light, coal tar, ammoniated mercury, anthralin, and topical corticosteroids. Methotrexate has been used to treat psoriasis by systemic administration, but such treatment method is accompanied by all the side effects commonly encountered with its use for other conditions. Antimetabolite drugs such as aminopterin, thioguanine, and azaribine have also been used in treating this disease. Systemic corticosteroids or anti-malarial drugs such as chloroquin may aggravate psoriasis by mechanisms that are not understood. A low relative humdity also aggravates the disease, probably by allowing desiccation of the skin and irritation.
It would, of course, be desirable to employ a topical treatment, for psoriasis, but according to Comaish and Juhlin, Arch. Dermatol. 100, 99 (1969) methotrexate, a drug of choice in severe cases, was not successful in treating psoriasis by the topical route. In fact, of the antimetabolite drugs, fluorouracil alone has been claimed to be effective in treating psoriasis by topical administration--see Z. Haut-Geschlechtskrankh 44, 361 (1969).
Mycophenolic acid is produced by various strains of fungi of the Penicillium brevicompactum, Penicillium stoloniferum and Penicillium urtichae groups. The compound was the first biologically-active compound isolated from a mold. The initial isolation was carried out by Gosio in 1896 (Gosio, Rivista d'Igiene e Sanita' pubblica, Ann. 7, 825, 869, 961 [ 1896]. Structure work was effected largely through the efforts of Raistrick et al. from 1932 to 1935 (Raistrick et al., Biochem. J. 26, 1441 [ 1932]; Biochem J. 27, 654 [ 1933]).
Mycophenolic acid is known to exhibit antifungal, antiviral and antibacterial activity. [See for example, J. Gen. Virol. 4, 629 (1969); J. Antibiotics, 22, 297 (1969).]
Mycophenolic acid .beta.-D-glucuronide is described by Ando et al. in J. Antibiotics, 23, 408 (1970) and its antitumor activity is set forth in that same article.